Plasticity of the Leishmania genome leading to gene copy number variations and drug resistance

F1000Res. 2016 Sep 20:5:2350. doi: 10.12688/f1000research.9218.1. eCollection 2016.

Abstract

Leishmania has a plastic genome, and drug pressure can select for gene copy number variation (CNV). CNVs can apply either to whole chromosomes, leading to aneuploidy, or to specific genomic regions. For the latter, the amplification of chromosomal regions occurs at the level of homologous direct or inverted repeated sequences leading to extrachromosomal circular or linear amplified DNAs. This ability of Leishmania to respond to drug pressure by CNVs has led to the development of genomic screens such as Cos-Seq, which has the potential of expediting the discovery of drug targets for novel promising drug candidates.

Keywords: Cos-Seq; Drug Resistance; Leishmania; Mode of action; Ploidy.

Publication types

  • Review

Grants and funding

BP is supported by grants from the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, and the Ministère du Developpement Économique de l’Innovation et de l’Exportation du Québec. MO is supported by grants from the Canadian Institutes of Health Research and holds a Canada Research Chair on Antimicrobial Resistance.